Solutions of micelle-forming surfactants are releasably enclosed in receptacles comprising microporous cellulose membranes to provide controlled release articles. The membrane is initially fashioned from an acylated cellulose membrane precursor which is thereafter deacylated to cellulose using an ammonia solution. By the present invention, electrolytes are added to the ammonia solution, whereby osmotic rupture of the membrane or membrane precursor by the enclosed surfactant solution during the deacylation process is avoided.
The copending application of Robert G. Laughlin, Serial No. 560,020, filed March 19, 1975, now abandoned in favor of continuation application 714,540, filed August 16, 1976, relates to the preparation and use of controlled release articles which comprise a solution of a micelle-forming surfactant contained in a receptacle, at least one portion of the wall of said solution-containing receptacle comprising a microporous cellulose membrane. Such articles are useful, for example, in the controlled release of biologically active surfactants to provide vaginal contraceptives.
In most instances, enclosing a solution of a water-soluble material within a microporous membrane such as cellulose can lead to osmotic rupture of the membrane during exposure to an external environment having a different concentration of solute therein. In the case of the micelle-forming surfactants, however, the osmotic pressure across the membrane is relatively low due to the association of surfactant monomers into micellar structures. For this reason, stable articles comprising a microporous cellulose membrane releasably enclosing a solution of a micelle-forming surfactant can be provided.
Cellulose, itself, cannot be cast into microporous membranes for use in the foregoing type of controlled release article. Rather, cellulose is first converted into an acylated derivative, most preferably cellulose acetate, which can be suitably cast. The cellulose acetate is used in the preparation of the receptacle, to which is added the surfactant. The cellulose acetate is thereafter deacetylated with ammonia to provide the microporous cellulose membrane through which surfactant monomers diffuse in a controlled manner. (The deacetylation of cellulose acetate to cellulose with ammonia is a well-recognized organic chemical technique.)
When preparing articles of the foregoing type, it has been determined that the ammonia used to deacetylate the enclosing cellulose acetate (or, more broadly, acylated cellulose) membrane precursor somehow disrupts the micellar structure of the surfactant solution so that substantially greater amounts of free surfactant monomer are present than in the absence of ammonia. The presence of surfactant monomer in solution in the article causes a marked increase in osmotic pressure, with attendant rupture of the membrane precursor or membrane which is ultimately formed.
It has now been discovered that the addition of electrolyte to the ammonia solution used to deacetylate cellulose acetate prevents osmotic rupture of the membrane precursor or membrane. While not intending to be limited by theory, it appears that the presence of electrolyte somehow overcomes the disruptive effect of ammonia on the surfactant micelles so that substantial amounts of monomer are not formed during the deacetylation reaction. Whatever the reason, the present invention provides an improved means for preparing controlled release articles comprising a solution of micelle-forming surfactant and a microporous cellulose membrane.